(-)-Zuonin A
(Synonyms: 表加巴辛,D-Epigalbacin) 目录号 : GC60393
(-)-ZuoninA(D-Epigalbacin)是一种天然木质素，是有效的、选择性的JNKs抑制剂，对JNK1、JNK2和JNK3作用的IC50值分别为1.7μM,2.9μM和1.74μM。
Cas No.:84709-25-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
(-)-Zuonin A (D-Epigalbacin), a naturally occurring lignin, is a potent, selective JNKs inhibitor, with IC50s of 1.7 μM, 2.9 μM and 1.74 μM for JNK1, JNK2 and JNK3, respectively[1].
(-)-zuonin A binds the D-recruitment site (DRS) of JNK, a recruitment site utilized by substrates and other substrates to dock onto and recognize MAPKs[1].(-)-zuonin A inhibits JNK activation by MKK4 and MKK7 and it inhibits substrate phosphorylation[1].
[1]. Tamer S. Kaoud, et al. Manipulating JNK Signaling with (-)-zuonin A. ACS Chem Biol. 2012 Nov 16; 7(11): 1873-1883.
| Cas No. | 84709-25-1 | SDF | |
| 别名 | 表加巴辛,D-Epigalbacin | ||
| Canonical SMILES | C[C@H]1[C@@H](C)[C@@H](C2=CC=C(OCO3)C3=C2)O[C@@H]1C4=CC=C(OCO5)C5=C4 | ||
| 分子式 | C20H20O5 | 分子量 | 340.37 |
| 溶解度 | 储存条件 | 4°C, protect from light | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.938 mL | 14.6899 mL | 29.3798 mL |
| 5 mM | 0.5876 mL | 2.938 mL | 5.876 mL |
| 10 mM | 0.2938 mL | 1.469 mL | 2.938 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Manipulating JNK signaling with (--)-zuonin A
ACS Chem Biol 2012 Nov 16;7(11):1873-83.PMID:22916726DOI:10.1021/cb300261e.
Recently, in a virtual screening strategy to identify new compounds targeting the D-recruitment site (DRS) of the c-Jun N-terminal kinases (JNKs), we identified the natural product (-)-Zuonin A. Here we report the asymmetric synthesis of (-)-Zuonin A and its enantiomer (+)-zuonin A. A kinetic analysis for the inhibition of c-Jun phosphorylation by (-)-Zuonin A revealed a mechanism of partial competitive inhibition. Its binding is proposed to weaken the interaction of c-Jun to JNK by approximately 5-fold, without affecting the efficiency of phosphorylation within the complex. (-)-Zuonin A inhibits the ability of both MKK4 and MKK7 to phosphorylate and activate JNK. The binding site of (-)-Zuonin A is predicted by docking and molecular dynamics simulation to be located in the DRS of JNK. (+)-Zuonin A also binds JNK but barely impedes the binding of c-Jun. (-)-Zuonin A inhibits the activation of JNK, as well as the phosphorylation of c-Jun in anisomycin-treated HEK293 cells, with the inhibition of JNK activation being more pronounced. (-)-Zuonin A also inhibits events associated with constitutive JNK2 activity, including c-Jun phosphorylation, basal Akt activation, and MDA-MB-231 cell migration. Mutations in the predicted binding site for (-)-Zuonin A can render it significantly more or less sensitive to inhibition than wild type JNK2, allowing for the design of potential chemical genetic experiments. These studies suggest that the biological activity reported for other lignans, such as saucerneol F and zuonin B, may be the result of their ability to impede protein-protein interactions within MAPK cascades.
Elucidating binding modes of zuonin A enantiomers to JNK1 via in silico methods
J Mol Graph Model 2013 Sep;45:38-44.PMID:24001752DOI:10.1016/j.jmgm.2013.08.008.
Aberrant c-Jun N-terminal kinase (JNK) signaling is associated with a number of diseases, including neurological conditions and cancer. Enantiomers of the lignan zuonin A, (-)-Zuonin A and (+)-zuonin A bind isoforms of JNK with similar affinity and disrupt protein-protein interactions at JNK's D-recruitment site. Thus, they are of interest as lead non-ATP competitive inhibitors of the JNKs. While (-)-Zuonin A inhibits the activity of JNK toward c-Jun by 80% when saturating, (+)-zuonin A only inhibits by 15%. Molecular docking and molecular dynamics simulations were performed to gain a better understanding of how these inhibitors interact with JNK. The results of this study provide new insight into potential binding modes for (-)-Zuonin A and suggest that (-)-Zuonin A interacts with JNK via an induced fit mechanism near the highly conserved φA-X-φB recognition site. Binding of (+)-zuonin A to JNK displays no such dynamic feature. The different binding modes may help explain differences in the inhibitory properties of the enantiomers although further experimental work would be necessary to fully confirm this interpretation.
Two new compounds from Schisandra glaucescens
J Asian Nat Prod Res 2013;15(5):466-72.PMID:23614827DOI:10.1080/10286020.2013.784277.
One new lignan (7S,8R,7'R,8'R)-7-(3,4-methylenedioxyphenyl)-8,8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3',4'-methylenedioxyphenyl)-tetrahydrofuran (1), one new sesquiterpene 2-hydroxy-11,12-dehydrocalamenene (2), one new natural product erythro-1-(3,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane (3), and two known lignans (+)-anwulignan(erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane) (4) and ( - )-zuonin-A (5) were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated by spectroscopic methods. The cytotoxicity of compounds 1 and 2 was assayed.
Two new lignans and melanogenesis inhibitors from Schisandra nigra
J Nat Med 2016 Jul;70(3):460-6.PMID:27142263DOI:10.1007/s11418-016-1000-6.
An acetone extract from the stems of Schisandra nigra MAX. (Schisandraceae) exhibited significant inhibition of 3-isobutyl-1-methylxanthine (IBMX)-stimulated melanogenesis in murine B16 melanoma F10 cells. Fractionation and purification of the extract led to the isolation of two new tetrahydrofuran-type lignans, (+)-5-methoxyzuonin A (2) and kadlongirin C (3), along with eight known compounds (1, 4-10). The structures of the new compounds were determined by spectroscopic analyses. Of the isolated compounds (1, 3 -10), (+)-Zuonin A (1) showed remarkable inhibition of melanogenesis at concentrations without cytotoxicity in B16 melanoma F10 cells. (+)-Zuonin A (1) did not inhibit tyrosinase; however, Western blot analysis revealed that it decreased protein levels of tyrosinase and tyrosinase-related proteins (TRP)-1 and TRP-2 without changing phosphorylation level of cAMP response element-binding protein.
From in Silico Discovery to intra-Cellular Activity: Targeting JNK-Protein Interactions with Small Molecules
ACS Med Chem Lett 2012 Aug 6;3(9):721-725.PMID:23002419DOI:10.1021/ml300129b.
The JNK-JIP1 interaction represents an attractive target for the selective inhibition of JNK-mediated signaling. We report a virtual screening (VS) workflow, based on a combination of three-dimensional shape and electrostatic similarity to discover novel scaffolds for the development of non-ATP competitive inhibitors of JNK targeting the JNK-JIP interaction. Of 352 (0.13%) compounds selected from the NCI diversity set more than 22% registered as hits in a biochemical kinase assay. Several compounds discovered to inhibit JNK activity under standard kinase assay conditions also impeded JNK activity in HEK293 cells. These studies led to the discovery that the lignan (-)-Zuonin A inhibits JNK-protein interactions with a selectivity of 100-fold over ERK2 and p38 MAPKα. These results demonstrate the utility of a virtual screening protocol to identify novel scaffolds for highly selective, cell-permeable inhibitors of JNK-protein interactions.